Psychological stress has a staggering impact on society and plays a major role in alcoholism. The goal of the present study is to explore the mechanistic basis of the relationship between exposure to stress and subsequent sensitivity to ethanol in ILS and ISS mice. I hypothesize that the effects of stress on ethanol sensitivity are dependent on the genetic background of the individual, and that these genetic differences are related to individual differences in limbic-hypothalamic-pituitary-adrenal axis (LHPA) activation. To study the complex interactions between alcohol and stress, I will utilize ethanol sensitivity phenotypes including ethanol induced -loss of righting reflex, -hypothermia, and -low dose activation. Peripheral and central components of LHPA activity will be assessed by measurement of corticosterone and adrenocorticotropic hormone levels, and in situ hybridization of related gene expression in the paraventricular nucleus of the hypothalamus. The characterization of neural regions and pathways in which cellular activity is changed after exposure to alcohol and stress in mice will further inform studies in human populations to establish predictors of alcoholism in humans and ultimately develop more effective treatments. [unreadable] [unreadable] [unreadable]